The basic aim of the research plan is to study the interrelationships between the composition of the intracellular fluids and sodium transport across epithelia. Although the program is primarily based upon intracellular recording with ion-selective microelectrodes and reference micropipets, complementary studies will be performed with 3 1p nuclear magnetic resonance, electron probe X-ray microanalysis and computer simulations. In order to facilitate integration of the information obtained, most of the work will be conducted with a single epithelial model, split and whole frog skin. The principal objective will be to characterize the mode of apical sodium entry from the outer medium into the cell, and in particular to examine the putative role of intracellular sodium and calcium in regulating this entry. A second objective will be to define the electrokinetic and thermodynamic properties of the Na,K-exchange pump a the basolateral membranes. A third concern will be to examine the functional integration of the entire epithelium under three experimental conditions.